Additional Ganglion Plexus Ablation During Thoracoscopic Surgical Ablation of Advanced Atrial Fibrillation: Intermediate Follow-Up of the AFACT Study.

Ganglion Plexus Ablation in Advanced Atrial Fibrillation: The AFACT Study

Left Atrial Ganglion Ablation as an Adjunct to Atrial Fibrillation Surgery in Valvular Heart Disease

Quality of life improves after thoracoscopic surgical ablation of advanced atrial fibrillation: Results of the Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT) study

Background The AFACT study demonstrated that additional ganglionated plexus (GP) ablation in addition to thoracoscopic pulmonary vein isolation in patients with advanced atrial fibrillation (AF) did not significantly reduce late recurrence. However, its impact on early recurrence during the blanking period remains unclear. Methods This study is a sub-analysis of the AFACT cohort, which randomized 240 patients with advanced paroxysmal or persistent AF to undergo either GP ablation (targeting the four major GPs and the ligament of Marshall) or no GP ablation, in addition to pulmonary vein isolation. Follow-up at 10 days post-discharge was conducted for wound assessment, and symptomatic patients were encouraged to obtain additional rhythm recordings. Early recurrence was defined as AF recurrence within the 3-month blanking period, while late recurrence referred to AF recurrence beyond this period. We also analyzed very early recurrence at 0–12 days and 0–30 days. Cox proportional hazards models were used for risk assessment. Results Among 240 patients, the procedure was aborted in 2 patients, and 3 were excluded due to missing recurrence dates, resulting in a total of 235 patients included in the analysis. Among them, 71 experienced early recurrence, with 36 in the GP ablation group and 35 in the non-GP group. Early recurrence occurred in 23.94% (17/71) within the first 12 days, and 63.38% (45/71) within the first month. GP ablation suppressed recurrence within the first 12 days (HR = 0.28, 95% CI: 0.09–0.84, P = 0.02) (Figure 1). However, this effect diminished over time (1 month: HR = 0.82, 95% CI: 0.46–1.48, P = 0.51; 3 months: HR = 1.09, 95% CI: 0.68–1.73, P = 0.73). In the GP group, persistent AF (HR = 2.69, 95% CI: 1.18–6.15, P = 0.02) and left atrial volume index (LAVI) (HR = 1.02 per 10-ml increase, 95% CI: 1.00–1.04, P = 0.03) were associated with early recurrence, whereas these factors were not significant in the control group. Among patients who experienced early recurrence within the first month, those in the GP ablation group had a higher risk of late recurrence compared to the control group (HR = 3.41, 95% CI: 1.18–9.82, P = 0.02). However, this association weakened as the early recurrence window extended (0–60 days: HR = 2.22; 0–90 days: HR = 1.69). In contrast, among patients without early recurrence, GP ablation showed a trend of reducing late AF recurrence, but these differences did not reach statistical significance (P > 0.05). Conclusions GP ablation predominantly suppresses very early recurrence (≤12 days); however, its effect diminishes over time. Meanwhile, GP ablation significantly increases the risk of late recurrence in patients with early recurrence, particularly within the first month. This suggests that following GP ablation, early recurrence shifts from being trigger-driven (autonomic) to substrate-dependent.

Ablation for atrial fibrillation (AF) is a genuinely viable and increasingly used option for improving quality of life in patients with symptomatic drug-refractory AF. What is remarkable about the limited success achieved with these procedures is that progress has occurred despite a near complete lack of knowledge about what causes or maintains AF. Focal origins for AF were first demonstrated decades ago1–4 with topical application of acetylcholine to junctional tissues and atrial sites triggering AF. More recently, there has been convincing documentation of rapid tachycardia arising from the pulmonary veins inciting AF, thus supporting the concept of “trigger elimination” contributing to the success of pulmonary vein isolation. However, studies also support the presence of multiple reentrant circuits maintaining and possibly initiating AF.5, 6 The ablation era has taught us7–9 that in persistent and chronic AF, trigger elimination alone is not enough and that substrate modification is probably necessary to decrease the likelihood of reentrant wavelet continuance and thereby increase success rates. Even the most ardent supporter of either hypothesis recognizes the limitations of each. How can a focal source exist in this milieu indefinitely, producing and maintaining chronic AF, and how do multiple reentrant wavelets arise spontaneously? Article see p 384 In this issue of Circulation: Arrhythmia and Electrophysiology , Niu et al10 provide important, interesting, and novel insights into solving this age-old riddle using a previously unexplored angle-autonomic manipulation. Acetylcholine was used to induce AF in 31 canines. In 12 of the animal studies, propafenone was administered. They then ablated the ganglionated plexi (GP). Before ablation, AF could still be induced despite administration of propafenone. After ablation, there was a consistent pattern of electrogram organization and atrial synchronization. In addition, subsequent administration of propafenone resulted in the inability to induce atrial tachyarrhythmia. There are several …

Adjunctive ganglionic plexus (GP) ablation may increase the efficacy of pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF). Prior meta-analyses examining PVI with adjunctive GP ablation have included non-randomized trials and have included trials evaluating thorascopic epicardial ablation. The objective of this study is to perform a meta-analysis of randomized controlled trials (RCTs) comparing endocardial catheter-based PVI to PVI with adjunctive GP ablation. Summary odds ratio (OR) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed with I2 values. Sub-group analysis was performed comparing arrhythmia recurrence between patients with paroxysmal versus persistent AF at trial baseline. Meta-regressions were performed with mean left atrial diameter and left ventricular ejection fraction at trial baseline as the moderator variables. Five RCTs were identified including 814 patients: 406 PVI + GP ablation and 408 PVI alone. The mean age of participants was 56.5years and 74.7% were male. Four of these trials evaluated catheter-based endocardial ablation for a total of 574 patients: 289 PVI + GP ablation and 285 PVI alone. The odds of arrhythmia recurrence in patients undergoing adjunctive GP ablation with PVI compared with PVI alone were a reduced: odds ratio (OR) 0.58, 95% confidence interval (CI) 0.41-0.82, I2 = 40.2%. In the subgroup analysis, the odds of arrhythmia recurrence with adjunctive GP ablation were reduced in those with paroxysmal AF (OR 0.396, 95% CI 0.23-0.69, I2 = 0%). A non-significant trend to reduced arrhythmia recurrence was also observed in those with persistent AF (OR 0.726, 95% CI 0.475-1.112, I2 = 0%). When performing the meta-regression, increased left atrial diameter was associated with decreased treatment effect of adjunctive GP ablation (R2 index = 1.0, I2 = 0%). The addition of GP ablation to PVI was associated with reduced arrhythmia recurrence. Adjunctive GP ablation was more effective in paroxysmal AF and in patients with smaller atria. Larger RCTs are needed to confirm the efficacy of GP + PVI ablation.

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU Horizon 2020 SME Instrument. Background Epicardial ganglionated plexi (GP) play a significant role in the initiation and maintenance of atrial fibrillation. However, modulation of this effect, through GP ablation, has had limited success; outcomes being confounded by unnecessary atrial tissue ablation and inability to access and ablate all of the atrial GPs. Selective pulsed field ablation (PFA) of GPs, using epicardial access, provides the opportunity to better identify the role of GP ablation in the treatment of atrial fibrillation. Purpose This study aimed to assess the safety and feasibility of selective GP ablation in patients undergoing elective coronary artery bypass grafting (CABG). It was hypothesized that GP ablation would provide an acute extension of atrial tissue refractoriness, which constitutes its antiarrhythmic effect. Methods Using a monopolar, monophasic PFA system, atrial GPs were ablated in nineteen patients with or without atrial fibrillation, undergoing CABG. The Oblique Sinus GP, Right Superior GP, Transverse Sinus GP, Left Superior GP and Ligament of Marshall GP were each ablated with up to sixty PFA pulses of 1000 V amplitude and 100 µs pulse width. Atrial Effective Refractory Period (AERP) was measured before and after all GP ablations, at the left atrial appendage (LAA) and on the right atrium (RA). Patients were monitored through to discharge for post-operative atrial fibrillation (POAF). Results Complete ablation of the GPs was performed in nineteen patients (aged 63.4 ± 6.6 years, 63.1% male) immediately after sternotomy. Electric field pulses were ECG-gated, with energy delivery during the ventricular refractory period. All GP sites were successfully accessed and ablated; all patients progressed immediately to their planned elective surgery and were discharged on schedule. Procedure time, for all GP ablations and AERP measurements was in the range 35-45 minutes. Thirteen valid pre- and post-ablation datasets were obtained. AERP (LAA and RA combined) increased upon GP ablation on average by 23% (220 ± 46 ms pre-ablation versus 269 ± 59 ms post-ablation, p = 0.002). Four patients experienced POAF; there was no evident correlation between POAF and AERP data. Only three of the enrolled patients had a prior history of AF; none of these exhibited AF on 24-hour Holter monitoring at 3-month follow-up. Conclusions Selective epicardial PFA of GPs is feasible and safe. An acute increase in atrial tissue refractoriness is promising but further studies are required to see how this translates to longer term outcomes in symptomatic AF patients and in a percutaneous epicardial access setting.

Left atrial (LA) ganglionated plexi (GP) are part of the intrinsic cardiac autonomic nervous system and implicated in the pathogenesis of atrial fibrillation. High frequency stimulation is used to identify GP sites in humans. The effect of ablation on neural pathways connecting GPs in humans is unknown. Thirty patients undergoing LA ablation with autonomic modification were recruited. In patients with persistent atrial fibrillation, endocardial continuous high frequency stimulation identified GP sites producing AV block. After right lower GP ablation (N=5), 2 of 15 sites remained positive, whereas after ablation of other GPs (N=5), leaving right lower GP intact, all 19 sites remained positive (right lower GP versus other GP, P<0.005), indicating that neural pathways between LAGPs and the AV node are via the right lower GP. In 20 patients with paroxysmal atrial fibrillation, synchronized high frequency stimulation identified sites initiating pulmonary vein (PV) ectopy. After PV isolation (N=8), no sites remained positive. After local GP ablation (N=9), 3 of 14 sites remained positive, suggesting neural connections to the PV were disrupted by both PV isolation and GP ablation. Heart rate variability indices reduced significantly after right upper GP ablation alone, suggesting that neural pathways from the LA to the SA node travel via the right upper GP. We have demonstrated neural pathways connecting LA GPs with the PVs, AV node, and SA node. The effects of high frequency stimulation at GP sites can be prevented by ablating the GP site or the neural pathway. This further delineates the mechanism via which PV isolation prevents atrial fibrillation and highlights important caveats for autonomic modification end points.

Effect of ganglionated plexi ablation by high-density mapping on long-term suppression of paroxysmal atrial fibrillation – The first clinical survey on ablation of the dorsal right plexusus

CSPE Young Investigator Award Session

Ganglionated plexi (GP) is claimed to be potentially responsible for atrial fibrillation (AF). The efficacy and safety of GP ablation remains controversial. This meta-analysis aimed to assess the efficacy of procedure with or without ablation of GP. We included controlled clinical trials or randomized controlled trials comparing procedures of GP ablation plus pulmonary vein isolation (PVI), GP ablation plus Maze, or GP ablation alone (experimental arm), with PVI or Maze without GP ablation (control arm). The early episodes of atrial arrhythmia recurrence (early recurrence) and freedom from AF (primary efficacy endpoint) were estimated. Six trials with a total of 342 patients (172 per experimental arm, 170 per control arm) were included in the meta-analysis. Subgroup analysis demonstrated that there was no significant difference in early recurrence between additional GP ablation to PVI or Maze, and PVI or Maze without ablation of GP (P = 0.06). However, early recurrence was significantly higher after GP ablation alone, compared with PVI alone (P = 0.02). Freedom from AF recurrence was significantly improved by additional GP ablation to PVI and Maze, compared with PVI and Maze without ablation of GP (P < 0.01). However, it was significantly aggravated by GP ablation alone, compared with PVI alone (P = 0.006). The short and relatively long-term success rate of additional GP ablation to PVI or Maze is superior to PVI or Maze without ablation of GP. GP ablation alone is less effective than PVI alone for the treatment of AF. Future studies are necessary to establish and standardize the targeting sites, endpoints, and methods of GP ablation.

To determine efficacy of a new procedure combining epicardial bipolar radiofrequency (RF) pulmonary vein (PV) antrum isolation and ganglionated plexus (GP) ablation for treatment of atrial fibrillation (AF). PV antrum electrical isolation and GP ablation have each been associated with elimination of AF. Both of these can be performed epicardially in a single combined surgical procedure, which may have advantages over endocardial ablation. Twenty-one subjects entered a prospective evaluation of limited thoracotomy epicardial bipolar PV antrum isolation, verified by PV recordings, with GP ablation, guided by GP mapping. Procedural success was defined as freedom from AF and antiarrhythmic agents during 1 year of follow-up, including evaluation by prolonged continuous monitoring capable of detecting asymptomatic arrhythmias. All subjects had recordable PV potentials and GP activity prior to ablation. Circumferential epicardial bipolar RF eliminated PV potentials in 18 of 20 right and 14 of 20 left PV antra. This concurrently eliminated 79% of GP activity (125 of 159 active sites); nearly all remaining GP activity could then be eliminated using epicardial bipolar RF forceps. Fifteen of 20 (75%) subjects overall, and 14 of 16 (87.5%) subjects with paroxysmal or persistent AF had a successful procedure. Limited thoracotomy epicardial bipolar RF antrum isolation, verified by PV recordings, with GP ablation, guided by GP mapping, is effective treatment for AF and should be considered in patients with paroxysmal or persistent AF.

Clinical studies described the addition of ganglionated plexus (GP) ablation enhancing the efficacy of pulmonary vein isolation (PVI) for atrial fibrillation (AF) and contribution of epicardial adipose tissue (EAT) containing GP to AF initiation has been reported for its autonomic modulation. The aim of this study was to determine the amount of EAT surrounding the left atrium (LA) correlate with recurrence of AF after PVI plus GP ablation (GP-ABL). 17 patients with paroxysmal AF (age 58±10 years, BMI 24.1±2.2) underwent GP-ABL and PVI. The selective GP-ABL guided by localization using endocardial high frequency stimulation showing a vagal response. Total volume of EAT (EAT-total) and EAT volume around the LA (EAT-LA) were identified by threshold setting of −30 to 200 Hounsfield units in multi-slice computed tomography measurement, compared between 8 pts with AF recurrence (AF-Rec) and 9 pts without AF recurrence (No-Rec) during follow-up months of 6±4. Despite the similar BMI (23.4±2.2 vs 24.8±2.2) in both group, AF-Rec had a significantly greater EAT-LA than No-Rec (2.6±1.2 vs 0.9±0.4 cm3, p<0.01), and EAT-total, the distribution of EAT as EAT-LA/EAT-total were increased (82.5±33.9 vs 59.0±50.4 cm3, p=0.27, 3.0±1.1 vs 2.0±1.0%, p=0.07) in AF-Rec. In conclusion, evaluation of EAT-LA can distinguish the AF recurrence after PVI plus GP-ABL.

Ablation of Ganglionic Plexi During Combined Surgery for Atrial Fibrillation

This study aimed to explore the safety and effectiveness of selective cardiac autonomic ganglion plexus (GP) ablation on patients with bradyarrhythmia. The heart is controlled by its own intrinsic and central autonomic nerves. Increased cardiac vagal tone leads to sinus node dysfunction and atrioventricular conduction disorders, resulting in bradyarrhythmia. Pacemaker implantation can relieve the symptoms of arrhythmia caused by bradycardia, but it is not easy for patients to accept a pacemaker implantation as a form of treatment. Therefore, more and more attention has been paid to cardiac vagus nerve ablation. In this study, 20 patients who met the inclusion criteria of GP ablation in the First Affiliated Hospital of Xinjiang Medical University from November 2019 to June 2020 were enrolled. Biochemical and other related examinations along with electrophysiological examinations were conducted before ablation, and then cardiac GP ablation was performed. The patients were followed up 3 times at 3, 6, and 12 months after the operation. The minimum HR and mean HR were significantly increased after treatment with cardiac autonomic GP ablation (p<0.01). Moreover, the SDNN (Standard deviation of Normal-to-Normal Intervals) and RMSSD (Root mean square successive differences between successive R-R intervals) was significantly decreased after treatment with cardiac autonomic ganglion plexus ablation for 6 months and 12 months (p<0.01). Cardiac GP ablation is relatively simple and easy to implement in units that have performed radiofrequency ablation for bradyarrhythmias. This procedure can be performed without any new equipment. Some patients with bradycardia may not have a permanent pacemaker implantation and may go in for additional treatment options.